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Biomedical subjects

J Kelly

Publications and source records attributed to J Kelly.

At least 307 records · Page 17Linked to original sources

The uaY positive control gene of Aspergillus nidulans: fine structure, isolation of constitutive mutants and reversion patterns.

The product of the uaY gene of Aspergillus nidulans is necessary for the expression of at least eight genes coding for enzymes and permeases of the purine utilisation pathway. A detailed fine structure map has been constructed of this gene involving 13 presumed point mutations and eight deletions. Gene conversion of these deletions was demonstrated. A technique was devised to select for constitutive mutations and two were obtained which map within the uaY gene. We have shown that the most centromere proximal allele reverts to a number of different phenotypes. The properties of this allele suggest that it may map in the open reading frame of the uaY gene, in a domain that could be altered in a way that would differentially affect the expression of genes under uaY control.

Aspergillus nidulans↗

Clinical benefits of structural and functional changes with calcium antagonists.

Calcium antagonists have a large variety of pharmacologic effects in addition to those exploited clinically. All drugs used in the management of hypertension, including calcium antagonists, are coming under increasing scrutiny for the possible beneficial and adverse effects they may have on the circulation and risk factor profile. This is particularly because of concern about the relative resistance of coronary heart disease to antihypertensive drug treatment and the increasing interest in evaluating the impact of blood pressure-lowering drugs on surrogate endpoints such as left ventricular hypertrophy. Given the pharmacokinetic and pharmacodynamic heterogeneity of calcium antagonists, it may be wise to keep in mind the subtypes as exemplified by the prototypes nifedipine, diltiazem, and verapamil and to extrapolate from one type to another with great caution. The increased understanding of the diversity among calcium antagonists as well as the pathophysiology of hypertension and other vascular diseases promises an exciting future for calcium antagonists in cardiovascular therapeutics.

Calcium Channel Blockers↗

Fistulae of obstetric origin.

World Health Organization (WHO) estimates that in the developing countries 5 million women each year suffer severe maternal morbidity and high on this list is obstetric fistulae (vesico-vaginal and/or recto-vaginal). This article tries to explain why these fistulae still occur, comments on measures of prevention and how treatment might best be provided for those women who suffer from this terrible affliction.

Delivery, Obstetric↗

Effects of Yersinia enterocolitica infection on rabbit intestinal and colonic goblet cells and mucin: morphometrics, histochemistry, and biochemistry.

The effects of Yersinia enterocolitica on intestinal goblet cells were investigated in New Zealand white rabbits. Animals infected with Y enterocolitica were compared with weight matched and pair fed controls. Goblet cell hyperplasia developed in the distal small intestine of infected rabbits on day 1, in the mid small intestine on day 3, and in the upper small intestine on day 6. In all regions hyperplasia persisted throughout the 14 day study. The degree of hyperplasia was greater in the distal small intestine than the upper and mid regions. Goblet cells in the proximal colon of infected animals seemed to respond as those in the distal small intestine. Thus goblet cell hyperplasia developed more rapidly and to a greater extent in the ileocaecal region where mucosal injury was most severe. These changes resulted directly from Y enterocolitica infection since goblet cell numbers did not increase in pair fed controls. Histochemically, goblet cell mucins from infected rabbits were unchanged at either six or 14 days. Biochemical analysis, however, established that purified mucins from animals on day 6 after infection were less sialylated (in the small intestine) and more sulphated (in the small intestine and proximal colon). In addition, mucins from the distal small intestine and the proximal colon seemed to contain fewer but longer oligosaccharide chains.

Amino Acids↗

The areas of various surfaces in the human mouth from nine years to adulthood.

Surface area measurements of five regions of the oral cavity were made from study casts of 57 subjects with an age range from 9.3 to 19 years. While the longitudinal pattern of growth exhibited by the total of the five areas, when subgroups were compared, was characterized by a steady increase to around puberty (13 years), followed by a plateau, different areas showed different patterns of growth. Increase in the surface area of the teeth was associated with the eruption of the second and third molars, whereas the area of the buccal lingual mucosa continued to increase into adult life. The palate, buccal vestibular mucosa, and dorsum of the tongue demonstrated a typically skeletal pattern of growth, i.e., increase until puberty with a rapid cessation thereafter. The results of this study indicate the need for longitudinal data to further knowledge concerning growth of the oral cavity.

Adolescent↗

Establishing therapeutic programs in the public sector psychiatric hospital: rethinking the possibilities and priorities.

In public sector hospitals, many patient therapeutic needs are easily identified, but multiple variables present in the system obscure the planning and implementation to meet these needs. Contextual variables that hinder program development include the physical environment; patient population; lack of guiding treatment philosophy; inconsistent approach; staff limitations; resistance to change; morale issues; and bureaucratic impasses. Assessment of the system culture is essential; determining the possibilities and priorities of the system will aid in designing and implementing projects or programs.

Clinical Protocols↗

A pharmacokinetic study to evaluate the profile of droxicam in elderly healthy volunteers after a single oral dose of 20mg.

A single oral dose pharmacokinetic study in a group of 10 elderly healthy volunteers was performed to evaluate the pharmacokinetic profile and the potential effect of age on the absorption, distribution and elimination of droxicam. After complete medical screening, and informed written consent, one dose (20mg) of droxicam was administered to all volunteers, under medical supervision. A complete pharmacokinetic profile of the obtained blood plasma levels was evaluated over 120 hours. All volunteers completed the study and in none did droxicam cause intolerance or side effects. The results showed that droxicam absorption, distribution and elimination did not differ substantially from reference studies done with young healthy volunteers. The peak mean plasma concentration was at 10 hours 1.38 +/- 0.29 microgram/ml, declining slowly, reaching 0.24 +/- 0.20 microgram/ml at 120 hours, with a half life of 50.23 +/- 17.19 hours and an elimination rate constant of 0.015 +/- 0.005 microgram/ml.h-1. In comparison to the healthy, young volunteers, the variation was minimal. It can be concluded from this study that age causes minimal variations in the absorption and distribution of droxicam.

Administration, Oral↗

Solubilization and characterization of endothelin-1 receptors in rat cardiac tissue.

Adult rat cardiac endothelin-1 (ET-1) receptors were solubilized with 0.5% digitonin and then characterized. The receptors retained binding activity after solubilization. Binding was saturable (KD of 0.065 +/- 0.004 nM, Bmax of 94.6 +/- 4.5 fmol/mg protein; Hill coefficient of 0.987 +/- 0.017 n = 6) and pH dependent, with the binding increasing as the pH was decreased from 10 to 4, but decreasing dramatically as pH dropped to 2. Specifically bound [125I]-ET-1 was not dissociated by 2 x 10(-7) M unlabelled ET-1, but was dissociated by pH 10 and 2. Returning the pH to 7.4 restored the binding activity of the receptors. Unlabelled ET-1 (10(-12) - 10(-7) M) and sarafotoxin S6b(10(-12) - 10(-7) M) competed with [125I]-ET-1 for binding to the receptors.

Animals↗

"Pre-embryos".

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Beginning of Human Life↗

The cardiovascular effects of oral nifedipine and nicardipine: a double-blind comparison in healthy volunteers using transthoracic bioimpedance cardiography.

The cardiovascular effects of single oral doses of nifedipine (5 and 10 mg) and nicardipine (20 and 30 mg) were compared in a placebo controlled double-blind crossover study involving 8 healthy male volunteers. Two hours following drug administration stroke volume and cardiac index were measured non-invasively using transthoracic electrical bioimpedance cardiography during passive tilting, graded bicycle exercise, and recovery from exercise. Two separate experiments were performed in the absence of active drug to allow the reproducibility of the measurements to be assessed. Coefficients of variation (within experiment/between experiments) for cardiac index were 7.0%/19.9% at rest and 11.5%/9.3% at 180 W exercise. Both nifedipine and nicardipine increased stroke volume and cardiac index and reduced total peripheral resistance (mean blood pressure/cardiac index) at all times in the experiment. Reductions in peripheral resistance were similar for nifedipine 10 mg and nicardipine 20 mg but in these doses slightly larger increases in heart rate were produced by nifedipine, and in stroke volume and cardiac index with nicardipine. The study shows that the cardiovascular effects of nifedipine and nicardipine can be detected using impedance cardiography which is a simple, safe, and inexpensive technique. The differences between the effects of the two drugs were small. Although some were of statistical significance and are consistent with a less marked cardiodepressant effect for nicardipine, the clinical importance of these observations is uncertain. Further studies to examine the effect of oral nifedipine and nicardipine in patients with impaired ventricular function may be helpful in clarifying this tissue.

Administration, Oral↗

Selective expression of PDGF A and its receptor during early mouse embryogenesis.

Murine homologs of the PDGF A, PDGF B, and PDGF receptor alpha subunit genes were cloned. These were used, together with a mouse PDGF receptor beta subunit cDNA clone, to monitor gene expression in early postimplantation mouse embryos and in F9 embryonal carcinoma cells. RNAse protection analysis shows that PDGF A chain, but not B chain, mRNA is expressed in 6.5- to 8.5-day embryonic and extraembryonic tissues. Both alpha and beta receptor subunit mRNAs are expressed in early embryos, however, alpha subunit mRNA appears earlier and is more abundant than beta subunit mRNA. Undifferentiated F9 embryonal carcinoma stem cells express abundant levels of A chain, but not B chain, mRNA. Neither of the PDGF receptor genes is expressed in stem cells. Treatment with retinoic acid stimulates expression of both PDGF receptor genes. As in postimplantation mouse embryos, alpha receptor subunit mRNA appears earlier and is substantially more abundant than beta subunit mRNA. Collectively, these data demonstrate that the genes encoding the two chains of PDGF and their receptors are regulated independently during development and suggest that the two systems have some nonoverlapping functions in vivo. PDGF A, but not PDGF B, may be particularly important in modulating early events in mouse embryonic development.

Amino Acid Sequence↗

Hypereosinophilic syndrome with unusual cutaneous manifestations in two men with HIV infection.

We report two men with human immunodeficiency virus infection who had unusual cutaneous manifestations of hypereosinophilic syndrome, exfoliative erythroderma, and linear flagellate plaques. In the first patient the cutaneous disease was the initial manifestation, and in the second the skin was the only organ affected. We also describe a favorable response to systemic corticosteroids and to psoralen with UVA phototherapy in one patient.

Adrenal Cortex Hormones↗

Squamous carcinoma of the posterior pharyngeal wall.

We have reviewed a 12-year experience with 295 patients treated for squamous carcinoma of the pharynx in order to focus on 78 patients whose lesions arose in the posterior wall. Surgery was the definitive therapy for the primary tumor in 57 (73%), including 3 treatment groups. Thirty-two patients had limited resections that preserved the larynx, involving local excision (7 patients), anterior pharyngotomy (7 patients), lateral pharyngotomy (6 patients), median labiomandibular glossotomy (6 patients), or median mandibulotomy with paralingual extension (6 patients). The second group consisted of 21 patients with more extensive tumors who required a laryngectomy and complex reconstruction, often with postoperative radiotherapy. Finally, there were four patients who developed metachronous second primaries in the pharynx subsequent to a laryngectomy. All required flap reconstruction. Of the 21 patients whose primary treatment was radiotherapy, 5 had lesions that were implanted after access was provided by a mandibulotomy. Cumulative 5-year survival was 32% and ranged from 44% in those with favorable lesions to 15% in those with extensive tumors. Our experience highlights the variety of treatment approaches available in patients with pharyngeal carcinomas confined to the posterior wall. Surgery in this setting carries acceptable morbidity and yields survival rates that compare favorably with those achieved by external radiation therapy alone. Results in patients with extensive lesions still leave much to be desired, despite radical surgery and aggressive radiotherapy. Innovative brachytherapy techniques using surgery for access deserve further investigation.

Adult↗